Predictive validity of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition indicators to diagnose malnutrition tool in hospitalized adults: a cohort study.

BACKGROUND: The lack of a widely accepted, broadly validated tool for diagnosing malnutrition in hospitalized patients limits the ability to assess the integral role of nutrition as an input and outcome of health, disease, and treatment. OBJECTIVES: This study aimed to evaluate the predictive validity of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition (ASPEN) indicators to diagnose malnutrition (AAIM) tool and determine if it can be simplified. METHODS: A prospective cohort study was conducted from August 2019 to September 2022 with 32 hospitals in United States. At baseline, 290 adult patients were evaluated for a diagnosis of malnutrition using the AAIM tool, which assesses weight loss, inadequate energy intake, subcutaneous fat and muscle loss, edema, and hand grip strength. Healthcare outcomes were extracted from the medical record: composite incidence of emergency department (ED) visits and hospital readmissions within 90 d postdischarge; length of hospital stay (LOS); and Medicare Severity Disease Related Group (MS-DRG) relative weight (i.e., healthcare resource utilization). We used multilevel, multivariable negative binomial or generalized linear regression models to evaluate relationships between malnutrition diagnosis and healthcare outcomes. RESULTS: After adjusting for disease severity and acuity and sociodemographic characteristics, individuals diagnosed with severe malnutrition had a higher incidence rate of ED visits and hospital readmissions (incidence rate ratio: 1.89; 95% CI: 1.14, 3.13; P = 0.01), and individuals diagnosed with moderate malnutrition had a 25.2% longer LOS (95% CI: 2.0%, 53.7%; P = 0.03) and 15.1% greater healthcare resource utilization (95% CI: 1.6%, 31.9%; P = 0.03) compared with individuals with no malnutrition diagnosis. Observed relationships remained consistent when only considering malnutrition diagnoses supported by at least 2 of these indicators: weight loss, subcutaneous fat loss, muscle wasting, and inadequate energy intake. CONCLUSIONS: Findings from this multihospital study confirm the predictive validity of the original or simplified AAIM tool and support its routine use for hospitalized adult patients. This trial was registered at clinicaltrials.gov as NCT03928548 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT03928548).

Comparison of the nutrient composition of eggs produced in the Guatemalan highlands during the wet and dry seasons.

The potential of chicken eggs as a nutritionally complete protein and source of key micronutrients during the first 1000 days post-conception has been progressively recognized across the globe, particularly in resource-poor settings. Fluctuation of egg nutrient content by season is relatively unknown, which may influence international food composition databases and outcomes in intervention studies using egg supplementation. To better interpret the findings of The Saqmolo' Project, we conducted comprehensive nutrient analyses on eggs produced during the wet and dry seasons in the highlands of central Guatemala. We randomly collected 36 shell eggs from a local farm during both seasons, hard-boiled, and prepared them for transport to the United States, where they were pooled and assessed for their nutrient composition. Methods of the Association of Official Analytical Chemists, the American Oil Chemists Society, and the American Association of Cereal Chemists were utilized to determine total energy, moisture, ash, total protein, total fat, fatty acids, total carbohydrates, 12 vitamins, 11 minerals, and carotenoids, by season, in some instances with modifications. Differences in nutrient composition between de-shelled hard-boiled eggs collected between seasons were assessed using an analysis of variance (ANOVA) and Tukey's family error rate comparison test. Most nutrients in eggs produced in the highlands of central Guatemala differed negligibly (but statistically significantly) based on seasonality. Only vitamins A and E, folate, choline, and calcium fluctuated at clinically significant levels relative to the AI/RDA for infants 7-12 months. Total energy, protein, trans fatty acids, moisture, and vitamin D3 levels did not differ between seasons (p > .05). Further multi-year sampling is needed to examine how seasonal variation affects the nutrient composition of eggs. These data may be used to supplement existing national and regional food composition databases.

Moderate consumption of freeze-dried blueberry powder increased net bone calcium retention compared with no treatment in healthy postmenopausal women: a randomized crossover trial.

BACKGROUND: Preclinical studies suggest that blueberry consumption is associated with improved bone health. OBJECTIVES: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment. METHODS: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance. RESULTS: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions. CONCLUSIONS: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.

Crop, Host, and Gut Microbiome Variation Influence Precision Nutrition: An Example of Blueberries.

Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.

Evaluating the Implementation of Evidence-based Kidney Nutrition Practice Guidelines: The AUGmeNt Study Protocol.

Evidence-based nutrition practice guidelines (EBNPGs) inform registered dietitian nutritionist (RDN) care for patients with chronic kidney disease grade 5 treated by dialysis; however, there has been little evaluation of best practices for implementing EBNPGs. In this effectiveness-implementation hybrid study with a quasi-experimental design, United States RDNs in hemodialysis clinics will document initial and follow-up nutrition care for patients with chronic kidney disease grade 5 treated by dialysis using the Academy of Nutrition and Dietetics Health Informatics Infrastructure before and after being randomly assigned to a training model: (1) EBNPG knowledge training or (2) EBNPG knowledge training plus an implementation toolkit. The aims of the study include examining congruence of RDN documentation of nutrition care with the EBNPG; describing common RDN-reported EBNPG acceptability, adoption, and adaptation issues; and determining the feasibility of estimating the impact of RDN care on nutrition-related patient outcomes. The AUGmeNt study can inform effective development and implementation of future EBNPGs. Keywords: Chronic kidney diseases; medical nutrition therapy; implementation science; clinical practice guideline; nutrition care process terminology; dietitian.

Academy of Nutrition and Dietetics Nutrition Research Network: The Saqmolo' Project Rationale and Study Protocol for a Randomized Controlled Trial Examining the Influence of Daily Complementary Feeding of Eggs on Infant Development and Growth in Guatemala.

Adequate nutrition during the complementary feeding period is critical for optimal child growth and development and for promoting long-term educational attainment and economic potential. To prioritize limited public health resources, there is a need for studies that rigorously assess the influence of multicomponent integrated nutrition interventions in children younger than age 2 years in different contexts. This study aimed to describe the rationale and protocol for the Saqmolo' Project using the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. The Saqmolo' (ie, "egg" in the Mayan language, Kaqchiquel) Project is an individually randomized, partially blinded, controlled comparative effectiveness trial to evaluate the influence of adding delivery of a single whole egg per day to local standard nutrition care (ie, growth monitoring, medical care, deworming medication, multiple micronutrient powders for point-of-use food fortification [chispitas], and individualized complementary and responsive feeding education for caregivers) for 6 months, compared with the local standard nutrition care package alone, on child development, growth, and diet quality measures in rural indigenous Mayan infants aged 6 to 9 months at baseline (N = 1,200). The study is being executed in partnership with the Wuqu' Kawoq/Maya Health Alliance, a primary health care organization located in central Guatemala. Primary outcomes for this study are changes in global development scores, assessed using the Guide for Monitoring Global Development and the Caregiver Reported Child Development Instruments. Secondary outcomes include changes in infant hemoglobin, anthropometric measures (including z scores for weight for age, length for age, weight for length, and head circumference for age), and diet quality as measured using the World Health Organization's infant and young child feeding indicators. The results of the Saqmolo' Project may help to inform public health decision making regarding resource allocation for effective nutrition interventions during the complementary feeding period.

Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.

Perspective: Planning and Conducting Statistical Analyses for Human Nutrition Randomized Controlled Trials: Ensuring Data Quality and Integrity.

Appropriate planning, execution, and reporting of statistical methods and results is critical for research transparency, validity, and reproducibility. This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition randomized controlled trials (RCTs). Readers are referred to the other NURISH (NUtrition inteRventIon reSearcH) publications for detailed information about the preparation and conduct of human nutrition RCTs. Collectively, the NURISH series outlines best practices for conducting human nutrition research.

Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response.

There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (ß-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. © 2020 American Society for Bone and Mineral Research (ASBMR).

Spot Urine Samples to Estimate Na and K Intake in Patients With Chronic Kidney Disease and Healthy Adults: A Secondary Analysis From a Controlled Feeding Study.

OBJECTIVE: The objective of this study was to assess the agreement between estimated 24-hour urinary sodium excretion (e24hUNa) and estimated 24-hour urinary potassium excretion (e24hUK), calculated from a spot urine sample using several available equations and actual sodium and potassium intake from a controlled diet in both healthy participants and those with chronic kidney disease (CKD). DESIGN AND METHODS: This study is a secondary analysis of a controlled feeding study in CKD patients matched to healthy controls. Participants (n = 16) consumed the controlled diet, which provided ∼2400 mg Na/day and ∼3000 mg K/day, for 8 days. On days 7 and 8, participants consumed all meals and collected all urine in an inpatient research setting, and they were discharged on day 9. The day 7 morning spot urine sample was used to calculate e24hUNa and e24hUK, which was compared with known sodium and potassium intake, respectively. RESULTS: Average e24hUNa from the INTERSALT and Tanaka-Na equations were higher than actual sodium intake by 373 mg and 559 mg, respectively, though the differences were not significant. e24hUNa from the Nerbass-SALTED equation in CKD participants was significantly higher than actual sodium intake by ∼2000 mg (P < .001), though e24hUNa from the Nerbass-RRID equation was not different from intake. e24hUK from the Tanaka-K equation was significantly lower than actual potassium intake (P < .001). For both e24hUNa and e24hUK for all participants, agreement with actual intake was poor, and e24hUNa and e24hUK were not correlated with actual sodium or potassium intake, respectively. CONCLUSION: e24hUNa and e24hUK are poor indicators of true sodium and potassium intake, respectively, in both healthy and CKD participants. Findings should be confirmed in larger sample sizes with varying levels of dietary sodium and potassium.

Perspective: Laboratory Considerations and Clinical Data Management for Human Nutrition Randomized Controlled Trials: Guidance for Ensuring Quality and Integrity.

In human nutrition randomized controlled trials (RCTs), planning, and careful execution of clinical data collection and management are vital for producing valid and reliable results. In this article, we provide an overview of best practices for biospecimen collection and analyses, and for the fundamentals of clinical data management, including preparation and study startup; data collection, entry, cleaning, and authentication; and database lock. The reader is also referred to additional resources for information to assist in the planning and conduct of human RCTs. The tools and strategies described are expected to improve the quality of data produced in human nutrition research that can, therefore, be used to support food and nutrition policies.

High folic acid or folate combined with low vitamin B-12 status: potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES.

BACKGROUND: Potential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status. OBJECTIVES: We aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of "high" folate status. METHODS: Cross-sectional data from older adults (≥60 y; n = 2420) from the 2011-2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12 < 150 pmol/L. Logistic regression models estimated ORs of scoring low on 1 of 4 cognitive tests: the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning tests, and the Animal Fluency test (AF). RESULTS: A significant interaction was observed relative to scoring low on the DSST (<34; UMFA; P-interaction = 0.0071) and AF (serum folate; P-interaction = 0.0078) for low vitamin B-12 and high folate status. Among those with low vitamin B-12, high UMFA or high serum total folate was associated with higher risk of scoring low on the DSST (OR: 2.16; 95% CI: 1.05, 4.47) and the AF (OR: 1.93; 95% CI: 1.08, 3.45). Among those with "normal" vitamin B-12, higher UMFA or serum total folate was protective on the CERAD-DR. In noninteraction models, when high folate and normal vitamin B-12 status was the reference group, low vitamin B-12 combined with high UMFA was associated with greater risk based on the DSST (<34, OR: 2.87; 95% CI: 1.85, 4.45; <40, OR: 2.22; 95% CI: 1.31, 3.75) and AF (OR: 1.97; 95% CI: 1.30, 2.97); but low vitamin B-12 and lower UMFA (OR: 1.69; 95% CI: 1.16, 2.47) was also significantly associated for DSST < 40 risk. CONCLUSIONS: Low vitamin B-12 was associated with cognitive impairment both independently and in an interactive manner with high folate for certain cognitive performance tests among older adults.

Dairy intake is not associated with improvements in bone mineral density or risk of fractures across the menopause transition: data from the Study of Women's Health Across the Nation.

OBJECTIVE: Menopause represents a period in which bone deterioration is accelerated; thus, primary prevention strategies to address age-related bone loss are crucial. Dairy products contain more than a dozen essential nutrients, including calcium, phosphorus, vitamin D, and high-quality protein, as well as bioactive compounds that may promote bone mineralization. However, the relationship between dairy consumption and bone health across the menopause transition remains largely unknown. The purpose of this analysis was to estimate the change in lumbar spine and femoral neck bone mineral density and the risk of bone fracture by the frequency of dairy intakes among women across the menopausal transition using the publicly available data from the Study of Women's Health Across the Nation. METHODS: We analyzed total dairy foods in four categories of <0.5, 0.5 to <1.5, 1.5 to <2.5, and ≥2.5 servings/d or <1.5 and ≥1.5 servings/d. A general linear model was used to estimate the association of dairy intake with the 10-year bone mineral density loss rate and a linear mixed model was used to estimate the annualized bone mineral density loss rate of the femoral neck and lumbar spine. A Cox proportional hazard model was applied to calculate hazard ratios and 95% confidence intervals of the nontraumatic fractures. Poisson regression was used to determine the relative risks and 95% confidence intervals of the nontraumatic fractures. The models were controlled for race/ethnicity, age, height, weight, smoking status, physical activity, alcohol consumption, calcium use, menopausal status, and total caloric intake. RESULTS: No significant differences in bone mineral density change were observed, regardless of baseline menopausal status. No significant differences in the risk of nontraumatic fracture were observed. CONCLUSIONS: In this group of US women undergoing the menopausal transition, dairy food intake was neither associated with femoral and spine bone mineral density loss nor the risk of fractures.

Calcium Supplement Use Is Associated With Less Bone Mineral Density Loss, But Does Not Lessen the Risk of Bone Fracture Across the Menopause Transition: Data From the Study of Women's Health Across the Nation.

Diet is a modifiable factor that is related to bone mass and risk for fractures; however, the use of calcium supplements for bone health is controversial, with little scientific agreement. The purpose of this analysis was to estimate the change in lumbar spine and femoral neck BMD and the risk of bone fracture by the use of calcium supplements among the Study of Women's Health Across the Nation (SWAN) participants. SWAN is a multicenter, multiethnic, community-based longitudinal cohort designed to examine the health of women across the menopause transition (n = 1490; aged 42 to 52 years at baseline in 1996 to 1997 and followed annually until 2006 to 2008). A mixed-effect model for repeated measures was used to estimate annualized BMD change across time between supplement users and nonusers, unadjusted or fully adjusted (age, race, height, weight, menopausal status [pre-, early peri-, late peri-, and postmenopausal], DXA scanner mode, alcohol intake, vitamin D supplement use, smoking, and physical activity) and a log-linear model with repeated measures was used to estimate the relative risk of fracture by calcium supplement use. All models were also stratified by baseline menopausal status. In fully adjusted models, calcium supplement use was associated with less annualized loss of femoral neck BMD (-0.0032 versus -0.0040 g/cm2/year; p < .001) and lumbar spine BMD (-0.0046 versus -0.0053 g/cm2/year, p = 0.021) in the complete cohort. However, this protective association of calcium supplement use with BMD loss was significant only among premenopausal women (femoral neck: -0.0032 versus -0.0042 g/cm2/year; p = 0.002; lumbar spine: -0.0038 versus -0.0050 g/cm2/year, p = 0.001); no significant differences in BMD were observed among women who were early perimenopausal by calcium supplement use at baseline. No significant differences in the relative risk of fracture were observed, regardless of baseline menopausal status. The use of calcium supplements was associated with less BMD loss over more than a decade, but was not related to the risk of incident bone fracture across the menopause transition. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Adiposity, Insulin Resistance, and Bone Mass in Children and Adolescents.

Context: Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship. Objective: To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents. Design: Cross-sectional secondary analysis of baseline data from a previous randomized trial. Setting: University research facility. Participants: A total of 240 adolescents (68% female), aged 7 to 15 years. Main Outcome Measures: Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance. Results: Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR. Conclusions: These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Mineral Intake Ratios Are a Weak but Significant Factor in Blood Pressure Variability in US Adults.

Background: Hypertension contributes substantially to chronic disease and mortality. Mineral intakes can modify blood pressure. Objective: Individual minerals and their intake ratios in US adults and their association with blood pressure were examined. Methods: Regression models were used to examine the associations of sodium, potassium, and calcium intakes and their ratios from food and supplements with blood pressure in 8777 US adults without impaired renal function from the 2011-2014 NHANES. We evaluated men (n = 4395) and women (n = 4382) separately. Models for predicting blood pressure were developed using age, blood pressure medication, race, body mass index (BMI), and smoking as explanatory variables. Results: Few adults met the recommended intake ratios for sodium:potassium (1.2% and 1.5%), sodium:calcium (12.8% and 17.67%), and sodium:magnesium (13.7% and 7.3%) for men and women, respectively. Approximately half of adults (55.2% of men and 54.8% of women) met calcium:magnesium intake ratio recommendations. In our regression models, the factors that explained the largest amount of variability in blood pressure were age, blood pressure medication, race/ethnicity, BMI, and smoking status. Together, these factors explained 31% and 15% of the variability in systolic blood pressure in women and men, respectively. The sodium:potassium (men and women), sodium:magnesium (women), and sodium:calcium (men) intake ratios were positively associated with systolic blood pressure, whereas calcium intake was inversely associated with systolic blood pressure in men only. When mineral intake ratios were added individually to our regression models, they improved the percentage of variability in blood pressure explained by the model by 0.13-0.21%. Conclusions: Strategies to lower blood pressure are needed. Lower sodium:potassium intake ratios provide a small benefit for protection against hypertension in US adults.

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development.

Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls). Out of 22 differentially methylated loci selected for validation by pyrosequencing, 19 loci with neighbouring CpG sites (probes) were confirmed in the pre-diagnostic study group and subjected to verification in a prospective cirrhotic cohort (13 cases, 23 controls). We established for the first time 9 probes that could distinguish HBV-negative cirrhotic patients who subsequently developed HCC from those who stayed cancer-free. These probes were identified within regulatory regions of BARD1, MAGEB3, BRUNOL5, FXYD6, TET1, TSPAN5, DPPA5, KIAA1210, and LSP1. Methylation levels within DPPA5, KIAA1210, and LSP1 were higher in prospective samples from HCC cases vs. cirrhotic controls. The remaining probes were hypomethylated in cases compared with controls. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established probes have potential to be developed into a routine clinical test after validation in larger cohorts.

Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier.

Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10-13 years were recruited for outcome assessments. Bone mineral content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months) (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03) and considering the entire study period (18 months) (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01). Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters.